L-asparaginase induces IP3R-mediated ER Ca²⁺ release by targeting µ-OR1 and PAR2 and kills acute lymphoblastic leukemia cells.

ABSTRACT: L-asparaginase is a standard therapeutic option for acute lymphoblastic leukemia (aLL), a hematologic cancer that claims the most lives of pediatric cancer patients. Previously, we demonstrated that L-asparaginase kills aLL cells via a lethal rise in [Ca²⁺]_i due to IP3R-mediated ER Ca²⁺ release followed by calpain-1-Bid-caspase-3/12 activation (Blood, 133, 2222-2232). However, upstream targets of L-asparaginase that trigger IP3R-mediated ER Ca²⁺ release remain elusive. Here, we show that L-asparaginase targets µ-OR1 and PAR2 and induces IP3R-mediated ER Ca²⁺ release in aLL cells. In doing so, µ-OR1 plays a major role while PAR2 plays a minor role. Utilizing PAR2- and µ-OR1-knockdown cells, we demonstrate that L-asparaginase stimulation

SUBMITTER: Lee JK 

PROVIDER: S-EPMC11327372 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature